Through its role as the organ of gas exchange, the lung is constantly exposed to microorganisms impacting the respiratory epithelial surface. The alveolar macrophages play a critical role in host defense through their ability to ingest and kill microorganisms. The ability of the alveolar macrophage to carry out this task can be enhanced by interferon-gamma, a mediator normally released by activated T-lymphocytes. Studies are ongoing in normals and asymptomatic individuals infected with the human immunodeficiency virus (HIV) to enhance lung host defense by administration of recombinant interferon-gamma by inhalation of an aerosol containing the interferon-gamma. In vitro studies are investigating the possibility of using techniques of gene transfer to modify the production of interferon-gamma autologous T-lymphocytes. Quantification of the levels of glutathione in HIV-seropositive individuals demonstrated a deficiency of this tripeptide in blood and lung, an observation relevant to the role of glutathione as an antioxidant, and in modulating immune function. Strategies have been developed to augment lung levels of glutathione by aerosol administration.